Hormones and Endocrinology Flashcards
Which hormones cross the membrane and which don’t?
Lipid soluble can cross
Water soluble require receptors to cross
Definition of hormones
Chemical messenger molecules that circulate in the blood and act on target cells
What is the difference between the endocrine, paracrine and autocrine response?
Endocrine - wen target cell is some distance away from the secretory cells
Pracrine- Target cell close/adjacent to secretory cell
Autocrine - released, hits target cell then loops back and binds to secretory cell to have negative feedback
Give examples of small chemicals/modifies amino acids
Dopamine
Adrenaline
Give examples of protein hormones
Oxytocin ADH Growth Hormone (somatotropin) Prolactin FSH TSH Insulin
Where are oxytocin and ADH produced?
Posterior pituitary
Where are Growth Hormone and Prolactin produced?
Anterior pituitary
What is the role of Growth Hormone?
Stimulates growth, cell division and regeneration
A mitogen - specific to certain types of cells
What is Prolactin?
198 residue protein (23kDa)
Closely related to GH and Placental Lactogen (PL) with properties and functions resembling both a hormone and cytokine
Where are FSH and TSH produced?
Anterior Pituitary
FSH and TSH are hetero-dimeric, what does this mean
Both parts bind to the receptor
Why can’t proteins be given by the oral route?
What other routes can be used?
Proteins get digested
Injection
Aerosols
Depot formulations
Which hormones are derived from Tyrosine?
Dopamine Noradrenaline Adrenaline T3 T4
Which hormones are derived from Tryptophan?
Melatonin
(derived from dietary tryptophan VIA serotonin
Where is serotonin converted to Melatonin?
Pineal Gland
What is structurally similar in steroid hormones?
All have teh same basic C17, 4 ring structure
Give examples of steroid hormones (lipid derived) and their C number
Oestradiol C18
Testosterone C19
Progesterone C21
Cortisol C21
What can aromatase (Anastazole) inhibitors be used for?
Patients with breast cancer (where tumour is oestrogen recpetor positive)
What are the two types of endocrine organs?
Primary - function is the secretion of hormones
Secondary - non-endocrine function
Where are the hypothalamus, pituitary and pineal glands?
Hypothalamus: below the thalamus, above the brain stem
Pituitary: in a small bone cavity below the hypothalamus
Pineal gland: epithalamus, between 2 hemispheres in the centre of the brain
Where are the hypothalamus, pituitary and pineal glands?
Hypothalamus: below the thalamus, above the brain stem
Pituitary: in a small bone cavity below the hypothalamus (sella turcica)
Pineal gland: epithalamus, between 2 hemispheres in the centre of the brain
What kind of hormones does the pineal gland produce?
Melatonin - helps regulate circadian rhythm
Where are the Thyroid and Parathyroid glands?
Neck region just beow the larynx
Sitting above and around the trachea
What does the thyroid gland produce and what do these do?
Produces T3 and T4
These help regulate metabolism
Produces calcitinin
This regilates production of calcium
What does the parathyroid gland produce and why?
PTH - parathyroid hormone
When biological signal goes down [Ca] - regulates
Where is the thymus?
Close to the heart
What happens in the thymus?
T-lymphocytes mature
What hormone does the thymus produce and what does this do?
Thymosin
Stimulates activity of T cells and antibody production in the bone-marrow
Which hormones are produces by the Islets of Langerhans (pancreas)?
Insulin Glucagon Somatostatin Ghrelin Pancreatic Polypeptide
How much of the pancreas is assciated with digestion and how much with endocrine function?
99% digestion
1% endocrine
What is hyposecretion (endocrine disorder)?
A gland does not produce enough of its hormones
What is hypersecretion (endocrine disorders)?
A gand produces too much of its hormone
What are the two tumour types that may develop in endocrine glands?
Malignant - cancerous
Benign - non-cancerous
Give examples of diseases caused by hypersecretion of hormones
Hyperinsulinsim
Cushing’s
Congenital Adrenal Hyperplasia
Graves’ disease
Give examples of diseases caused by hyposecretion of hormones
Diabetes
Hypothyroidism
Addison’s
Give examples of two types of endocrine gland tumours
Multiple Endocrine Neoplasia
Pheochromocytoma
Where are the adrenal glands and what are they responsible for?
On the top of the kidneys
Release hormones in response to stress
What are the two regions of the adrenal glands and which hormones do they release?
Central medulla - adrenaline and noradrenaline
Outer cortex - steroids e.g. cortisol
What effect does cortisol have on steroid synthesis
Negative
Which part of the brain detects stress?
Hypothalamus
What happens when cortisol is released?
Increase blood glucose
Has negative feedback
Which hormones do the ovaries secrete?
Steroids - oestrogen and progesterone
Protein hormones - inhibin and relaxin
What is the role of the ovaries?
Sexual development and reproduction
What are the ovaries regulated by?
Follicle stimulating hormone (FSH) Luteinizing hormone (LH)
Where are the testes located?
In the scrotum
Functions of the testes
Spermatogenesis Steroid hormones (androgens - mainly testosterone)
What are the testes regulate by?
FSH and LH
What is the role of the placenta?
Links developing feotus to the maternal uterine wall
Facilitates nutrient uptake, removal of waste products and gas exchange via the maternal blood supply
Which hormones does the placenta produce?
Steroids - oestrogen and progesterone
Protein - chorionic gonadotropin (CG), corticotropin releasing hormone (CRH), placental lactogenic (PL)
Which hormones does the placenta produce?
Steroids - oestrogen and progesterone
Protein - chorionic gonadotropin (CG), corticotropin releasing hormone (CRH), placental lactogenic (PL)
What hormone does the heart produce and what does it do?
Atrial natriuretic peptide (ANP)
Stimulates kidneys to secrete more salt = decreases excess blood volume (combating high BP and sodium concs)
How many hormones does the GIT produce?
30
What hormones do the kidneys secrete? What does it do?
Juxtaglomerular cells secrete renin
Renin indirectly signals adrenal cortex to secrete aldosterone
Erythropoietin signals bone marrow to increase RBC production
What hormones does the skin secrete?
Modified cholesterol with UV exposure becomes Vitamin D precursor
Vitamin D necessary for calcium metabolism - signals intestine to absorb calcium
What connects the pituitary gland to the hypothalamus?
Infundibulum
How does the anterior pituitary link to the hypothalamus?
Circulatory system link:
Parvicellular neurons secrete regulatory hormones into the bloodstream
These travel through the portal system to the AP - triggers secretion of other hormones
How does the posterior pituitary link to the hypothalamus?
Direct neuro-endocrine link:
Magnocellular neurons have long axons which extend down into the posterior pituitory lobe
What is PRH and what does it do?
Prolactin Releasing hormone (hypothetical)
Positive effect on the AP to produce prolactin which affects mammary development and lactation
What is PIH and what does it do?
Prolactin Inhibiting hormone (Dopamine)
Negative effect on the AP to reduce production of prolactin which affects mammary development and lactation
What is TRH and what does it do?
Thyrotropin Releasing hormone (TRH)
Positive effect on the AP to produce Thyroid Stimulating Hormone (TSH) causing secretion of thyroid hormones by thyroid gland
What is CRH and what does it do?
Corticotropin Releasing hormone (CRH)
Has a positive effect on the AP to produces Adrenocorticotropic hormone (CTH) which affects the Adrenal cortex so more production of steroid hormones
What is GHRH and what does it do?
Growth Hormone Releasing Hormone
Has a positive effect on the AP to produce more GH and increase growth and secretion of insulin like growth factors from the liver
What is GHIH and what does it do?
Growth Hormone Inhibiting Hormone (Somatostatin)
Has a negative effect on the AP to produce less GH and reduce growth and secretion of insulin like growth factors from the liver
What is GNRH and what does it do?
Gonadotropin Releasing Hormone (GNRH)
Has a positive effect on the AP to increase FSH and LH production and increase goads for the production of sex hormones
What are tropic hormones?
Act on another primary endocrine gland to produce effector hormones (Non-tropic act directly on other tissues)
Name all the anterior pituitary hormones
FSH LH Adrenocorticotropic hormone Thyroid Stimulating Hormone Prolactin Growth Hormone
What is the role of FSH and LH?
Sythesised, stored and secreted from the gonadotropes
Stimulates ovaries to produces oestrogen and testes to produce testosterone
LH - role in ovulation and corpus luteum growth. Stimulates androgen secretion by interstitial cells in testes
What is the role of ACTH?
Sythesised, stored and secreted from corticotropes
Stimulates adrenal gland cortex to produce corticosteroids such as aldosterone and cortisol
What is the role of TSH?
Sythesised, stored and secreted from the thyroid gland to produce T3 and T4
What is the most common pituitary tumour? How is this treated?
Prolactinoma
Dopamine receptor agonists (PIH) - bromocriptine, cabergoline
What is prolactin synthesized and secreted by?
Lactotropes
What is Growth Hormone synthesized and secreted by?
Somatotropes
What does hypersecretion of growth hormone cause in children?
Gigantism
What does hypersecretion of growth hormone cause in adults?
Acromegaly
What is used to treat acromegaly and how does it work?
Somatostatin (GHIH)
Regulates production of GH and affects cell proliferation and growth via somatostatin receptors
Why are synthetic analgues (Sandostatin) of somatostatin used?
They have a much longer half life
90 mins vs 3 mins
What can cause insufficient GH production?
Hypothalamic or pituitary tumour
Mutation of GH genes
Head injury or infection
Radiotherapy
What can cause GH resistance? (Laron dwarfism)
GH binding protein mutations
GH receptor mutations
How is somatropin produced?
Recombinant DNA technology
Which drug is used for severe hypopituitarism? (iv injection)
Protirelin
Which drug is used to treat endometriosis and infertility? (iv injection)
Gonadorelin
Which drug is used to treat pituitary diabetes insipidus? (injection)
Vasopressin
How does oxytocin differ from vasopressin
By two amino acids (Phe-Ile) (Arg-Leu)
What are the functions of axytocin?
Stimulates milk ejection
Stimulates smooth muscle contraction at birth
Establishment of maternal behaviour
What is the synthetis form of oxytocin?
Pitocin
What is the function of ADH?
Binds to receptors on collecting duct cells in kidney = synthesis and insertion of aquaporins into kidney tubules
Water reabsorption promoted
What are the two types of diabetes insipidus and how do they differ?
Hypothalamic (central) - deficiency in vasopressin secretion
Nephtogenic - kidney is insensitive to vasopressin
What is hypothalamic diabetes caused by?
Head trauma
Infections
Tumours involving hypothalamus
What is nephrogenic diabetes caused by?
Renal disease
Mutations in the vasopressin receptor gene or in the gene encoding aquaproin-2
How is hypothalamic diabetes treated?
Use and exogenous vasopressin
How is nephrogenic diabetes treated?
Increase water consumption
What do pinealocytes secrete?
Melatonin
What is production of melatonin inhibited by?
Light to the retina
What can melatonin be used to treat?
Seasonal affective disorder (SAD) and insomnia
What does the Zona Glomerulosa produce?
Mineralocorticoids - Aldosterone
What does the Zona Fasciculata produce?
Glucocorticoid - Cortisol
What does the Zona Reticularis produce?
Adrenal Androgens
Androstendiones
What is the rate limiting step of steroidogenesis?
Cholesterol to pregenolone
What are the physiological actions of Glucocorticoids?
Metabolic effects
Anti-inflammatory
Immunosuppressive
What are the physiological actions of Mineralcorticoids?
Water and Electrolyte balance
What are the physiological actions of Adrenal Androgens?
Maturation and Development
Which corticosteroid binding globulin binds cortisol and aldosterone?
Transcortin
Which steroids does transcortin not bind?
Synthetic steroids
Which steroids does albumin bind?
Synthetic and natural
What action do steroids have?
Changes in gene transcription and translation
Alter synthesis of specific proteins
What is the mechanism of mineralocorticoids?
Cause Na uptake leading to fluid reabsorption and K loss
What is the role of spironolactone?
Competitive inhibitor of MC receptors
Diuretic and antihypertensive
What actions does cortisol have?
Lipolysis Gluconeogenesis Protein catabolism Sensitising blood vessels Reduce inflammation Negative feedback
Give examples of short acting steroids and how long do they act for?
8-12 hours
Hydrocortisone
Fludrocortisone
Give examples of intermediate acting steroids and how long do they act for?
12-36 hours
Prednisolone
Give examples of long acting steroids and how long do they act for?
36-72 hours
Dexsmethasone
Betamethasone
Example of a mixed GC/MC activity steroid
Prednisolone
Example of a pure GC activity steroid
Dexamethasone
Betamethasone
Beclomethasone
Example of a mainly MC activity steroid
Fludrocortisone
How are steroids used in replacement therapy and which ones are used?
Addison’s Disease
Hydrocortisone (GC) with/without fludrocortisone (MC)
Congenital Adrenal Hyperplasia
Dexamethasone, betamethasone
What are the symptoms of Addison’s disease?
Appetite/weight loss Discolouration of skin Dehydration Increased thirst and urination Salt,soy sauce, liquorice cravings Oligomenorrhoea No energy or motivation Sore/painful, weak muscles and joints
What is congenital adrenal hyperplasia?
Fault in steroidogenesis pathway Overproduction of androgens Limited/no cortisol negative feedback ACTH output is raised So synthetic steroids are used to recover the missing feedback
How do steroids act as anti-inflammatories and immunosuppressants?
Give examples
They reduce mediators of inflammation and immune responses (prostaglandins, cytokines, NO, IgG)
Hydrocortisone, prednisolone, beclometasone, dexamethasone, budesonide
What can overuse of steroids lead to?
GC’s:
Drug induced Cushing’s syndrome
Osteoporosis
Increased risk of infection
Which drugs are used to target steroidogensis?
Aminoglutethimide
Metyrapone
Tetracosatide/Stnacthen
What does aminoglutethimide do and what is it used for?
Inhibits enzymes in steroid synthesis
Pregnenolone synthase
21-, 11B-, and 18-hydroxylase
Aromatase (E production from T)
Used:
Cushings
Postmenopausal Breast Cancer
Prostate cancer
What does Metyrapone do and what is it used for? what are the SE’s?
Inhibits 11B-hydroxylase
Reduced GC and MC synthesis
Used:
Cushings
Hyperaldosteronism
SE’s: hirsutism in women because of excess androgens
What does tetracosatide/synacthen do and what is it used for?
Synthetic peptide and ACTH analogue
Stimulates synthesis and release of adrenal hormones
Used to diagnose adrenal cortical insufficiency
